A randomized trial of bariatric surgery for the treatment of sleep apnea

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）是肥胖最常见的并发症之一，导致过度嗜睡和日间功能障碍。此外，反复暴露于间歇性低氧血症似乎与肥胖协同作用，易患高血压、胰岛素抵抗、糖尿病、心血管疾病和中风。目前对中重度OSA的一线治疗，鼻腔持续气道正压通气（CPAP）非常有效，但通常耐受性不佳，导致许多患者的依从率低。减肥手术已被批准用于治疗阻塞性睡眠呼吸暂停的合并肥胖患者，在小病例系列中，似乎产生了实质性的改善。然而，目前还没有直接比较减肥手术与标准CPAP治疗的试验来指导临床医生和患者选择最合适的一线治疗。我们建议进行一项试点研究，以解决可行性和安全性问题，并估计随后的3期试验的效应量。我们将从两个大型临床睡眠项目中招募80名患有严重OSA和病态肥胖（体重指数，BMI, 35-40 kg/m2）的患者，这些患者共同护理广泛且人口统计学上不同的OSA患者群体。在建立患者和医生的平衡后，受试者将被随机分配到CPAP或腹腔镜胃束带作为OSA的一线治疗的试验中。主要结局指标将是在理想和现实生活条件下（即，在OSA组中，分别在受控环境中使用CPAP和在常规家庭环境中使用处方治疗）的OSA严重程度的改善，这将允许评估比较疗效和有效性。结果将在9个月时进行评估，以量化每种治疗策略的早期有效性，并在未来使用这两个组进行更大规模的长期试验时证明临床平衡。进一步的随访将在18个月后对40名患者进行，以确定在减肥组体重接近平台期时后续研究的效应大小。次要结果将包括与患者相关的结果，包括嗜睡、生活质量和卫生服务利用指数。此外，将评估每组中与炎症、胰岛素抵抗、血脂、血压和动脉僵硬相关的生物标志物的变化，以及与BMI和OSA变化的关系，为未来的试验确定有希望的结果措施。将收集所有科目的已发生费用，以便建立成本效益分析所需的参数。这项初步研究将首次对OSA的内科和外科治疗进行对照比较，此外，还将提供必要的数据，为随后的长期多中心比较有效性研究提供最佳研究设计，以更好地了解减肥手术在OSA管理中的潜在作用。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is one of the most common complications of obesity, resulting in excessive sleepiness and daytime functional impairment. In addition, the recurrent exposure to intermittent hypoxemia appears to act synergistically with obesity in predisposing to hypertension, insulin resistance, diabetes, cardiovascular disease, and stroke. The current first line treatment for moderate to severe OSA, nasal continuous positive airway pressure (CPAP) is extremely effective but is often not well tolerated, leading to low adherence rates in many patients. Bariatric surgery has been approved as treatment for OSA in patients with co-morbid obesity and in small case series, appears to produce substantial improvements. However, no trials directly comparing bariatric procedures with standard CPAP treatment yet exist to guide clinicians and patients in choosing the most appropriate first line treatment. We propose to conduct a pilot study to address the feasibility and safety, and estimate the effect sizes for a subsequent Phase 3 trial. We will recruit 80 patients with severe OSA and morbid obesity (body mass index, BMI, of 35-40 kg/m2) from two large clinical sleep programs that together care for a wide spectrum and demographically diverse group of OSA patients. After establishing patient and physician equipoise, subjects will be randomized to a trial of CPAP or laparoscopic gastric banding as first line treatment for OSA. The primary outcome measures will be improvement in OSA severity under both ideal and real life conditions (i.e., in the OSA arm, while using CPAP in a controlled environment vs. while using prescribed therapy in the usual home environment, respectively), which will allow for assessments of both comparative efficacy and effectiveness. Outcomes will be assessed at 9 months to quantify the early effectiveness of each treatment strategy as well as to demonstrate clinical equipoise in conducting a future larger long term trial using these two arms. Further follow-up will occur at 18 months in a subset of 40 patients to determine effect sizes for the subsequent study at a point where the bariatric arm has neared a plateau in weight. Secondary outcomes will include patient-related outcomes including sleepiness, quality of life, and an index of health service utilization. In addition, changes in biomarkers related to inflammation, insulin resistance, lipids, blood pressure, and arterial stiffness will be assessed in each group, and in relationship to changes in BMI and OSA, to identify promising outcome measures for future trials. Incurred costs will be collected in all subjects in order to establish the parameters needed for a cost effectiveness analysis. This pilot study will represent the first controlled comparison of medical and surgical treatments for OSA and in addition, will provide the necessary data to develop the optimal study design for a subsequent long term multi-center comparative effectiveness study to better understand the potential role that bariatric surgery may offer in the management of OSA.